Synergizing multimodal data and fingerprint space exploration for mechanism of action prediction

Effective computational methods for predicting the mechanism of action (MoA) of compounds are essential in drug discovery. Current MoA prediction models mainly utilize the structural information of compounds. However, high-throughput screening technologies have generated more targeted cell perturbation data for MoA prediction, a factor frequently disregarded by the majority of current approaches. Moreover, exploring the commonalities and specificities among different fingerprint representations remains challenging.

In this paper, we propose IFMoAP, a model integrating cell perturbation image and fingerprint data for MoA prediction. Firstly, we modify the Res-Net to accommodate the feature extraction of five-channel cell perturbation images and establish a granularity-level attention mechanism to combine coarse- and fine-grained features. To learn both common and specific fingerprint features, we introduce an FP-CS module, projecting four fingerprint embeddings into distinct spaces and incorporating two loss functions for effective learning. Finally, we construct two independent classifiers based on image and fingerprint features for prediction and for weighting the two prediction scores. Experimental results demonstrate that our model achieves highest accuracy of 0.941 when using multimodal data. The comparison with other methods and explorations further highlights the superiority of our proposed model and the complementary characteristics of multimodal data.

The source code is available at https://github.com/ s1mplehu/IFMoAP. The raw image data of Cell Painting can be accessed from Figshare (https://doi.org/10.17044/scilifelab.21378906).